This investigation has as its goal the design and synthesis of a series of 3'-deoxy pyrimidine and purine nucleoside analogs, and some of their nucleotide addition, the 2', 3'-unsaturated, 2', 3'-dideoxy-ara-C derivatives of 3-deazacytidine will be synthesized and evaluated as potential anti-HIV and anti-CMV agents. The approaches to be employed include the development of methodology mass spectrum, and other spectroscopic techniques, and the determination of their biological and biochemical effects. Recently, a lead compound, 1-(3-deoxy-B-D-threopentofuranosyl) cytosine (3'-deoxy-ara-C), has been synthesized and evaluated for its antiviral activity in this laboratory. Our preliminary studies have shown that 3'- deoxy-ara-C not only has potent anti-HCMV activity (ED50 = 0.31 ug/mL vs ED50 = 0.92 ug/mL for DHPG), but also is structurally different from DHPG. Based on these findings, the 5'-mono- and triphosphates of 3'-deoxy-ara-C will be prepared for biochemical studies. The understanding of the mechanism of action of 3'-deoxy-ara-C may lead to the design and synthesis of new antiviral agents with a better therapeutic index.